This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Infections caused by group A streptococci (GAS) lead to a wide spectrum of diseases, ranging from relatively benign conditions to invasive diseases and serious nonsuppurative sequelae, such as acute rheumatic fever (ARF). While the incidence of ARF has declined dramatically in industrialized countries, ARF remains the leading cause of acquired heart disease among children in many developing countries. For unknown reasons, the annual incidence rate of ARF in Hawaii has continued to be 40-fold higher than that on the continental U.S., particularly among native Hawaiians and other Polynesian ethnic groups. Preliminary studies indicate that pharyngeal infection-associated GAS M protein serotypes (the so-called rheumatogenic types), which are known to be associated with ARF, are infrequently isolated from ARF patients in Hawaii. Instead, unusual M types of GAS have been identified in local patients with ARF or with invasive and non-invasive GAS diseases. The objective of this research project is to determine the molecular epidemiology and adhesion properties of GAS in native Hawaiians and other Polynesian groups. The central hypothesis is that pharyngeal carriage of skin-associated and unusual M types of GAS accounts for high-incidence ARF and other streptococcal diseases in Hawaii. The proposed five-year study will test our hypothesis by pursuing the following specific aims: 1. Characterize the GAS in Hawaii and evaluate the epidemiologic factors that correlate with the high incidence of ARF in native Hawaiians and other Polynesian ethnic groups. 2. Assess the GAS pharyngeal carrier status in different ethnic groups, as well as the adhesion properties of GAS in carriers and patients with ARF and invasive GAS disease in Hawaii. This project is innovative because it will provide new knowledge about the diversity of GAS M proteins and their association with ARF and other streptococcal diseases and their sequelae. Our full expectation at the conclusion of this project is that we will know the diversity of M types in Hawaii. This information will have a significant impact on the development of vaccines for ARF and invasive and non-invasive GAS diseases.